It is already known that a number of metabolic toxins such as mercaptans, free fatty acids, unconjugated bilirubin and endotoxins of gram-negative bacteria as well as many exogenous toxins, specifically medications such as nortriptyline, amitryptiline, diazepam, bromazepam, etc., are almost completely bound to proteins in the bloodstream. They are bound preferentially to the albumin fraction of blood plasma. Because of the size of the molecules and the strong binding interaction of the protein-toxin complex, it is difficult or impossible to selectively remove from blood toxins bound to albumin by traditional blood purification methods such as hemodialysis.
However, there are already known blood purification methods with which protein-bound toxins can be removed from blood or plasma. A known method is hemoperfusion with activated carbon or ion exchange resins. These adsorber materials have measurable elimination rates for many protein-bound toxins (J. L. Rosenbaum et al. 1980: "Current status of hemoperfusion in toxicology." Clin. Toxicol. 17: 493). One disadvantage of the known adsorbents is that they have mostly nonspecific binding properties. Thus, in addition to the albumin-bound toxins, undesired hormones, growth factors and cells such as platelets are also removed, which can lead to side effects and complications.
World Patent WO 94/21363 describes a dialysis method with which albumin-bound substances can be removed from blood. An asymmetrical dialysis hollow fiber is coated with albumin essentially on the side facing away from the blood (in the porous supporting layer). In addition, the hollow fibers are rinsed with an albumin solution on the outside, with this albumin solution also being circulated through a cartridge of activated carbon or ion exchanger and passed through an additional dialyzer to remove the transported toxins from the dialysate. The toxin-laden albumin molecules of the blood are spatially separated from the toxin-free albumin molecules in the supporting layer by an internal albumin-impermeable dividing layer of dialysis fibers. The albumin-impermeable dividing layer is indispensable for the functioning of this arrangement to prevent back-diffusion of the essentially freely mobile toxin-albumin complexes and thus maintain a directional transport of toxins out of blood and into the dialysate.
To be removed from blood, the toxins must pass through the albumin-impermeable dividing layer. This is a disadvantage especially for removal of large toxin complexes such as endotoxin complexes of gram-negative bacteria, which cannot be removed from blood with the method described above. In addition, this arrangement also does not yield selective removal of substances because all substances which have such a small molecular size that they can pass through the inner dividing layer of the dialysis fibers can also be removed at the same time.
World Patent WO 95/04559 describes an arrangement with a membrane filter for eliminating toxins from protein-containing fluids, especially blood. The fluid to be purified, e.g., blood, is passed through the lumen of a hollow-fiber membrane filter around whose outside flows a purifying suspension containing solid particles to bind the toxins. The purifying suspension is kept in motion by a centrifugal pump, causing local variations in transmembrane pressure differences on the membrane filter, so there is a fluid exchange through the walls of the filter. Toxins transported with the fluid thus come in contact with the adsorbent particles, while at the same time purified fluid flows back into the blood stream. This arrangement also has the disadvantage that the toxin complexes must pass through the filter walls to be removed from the fluid to be purified.
An albumin-coated adsorber used to remove protein-bound metabolites or toxins from the blood is already known from J. of Clinical Investigation, vol. 53 (March 1974), pages 778-85. However, the known adsorber is neither hemocompatible nor steam sterilizable, so therapeutic use is impossible. Albumin is coupled via cyanogen bromide, which may adhere to the end product as an impurity and is a strong toxin even in low concentrations. The support material is also not suitable for preventing complement activation or platelet adhesion.